Liver and Bile
Hepatology. 2022;75(3):531–40
Effect of corticosteroid dosing on outcomes in high-grade immune checkpoint inhibitor hepatitis
Background and aims: Consensus guidelines recommend high-dose corticosteroids (1–2 mg/kg/day methylprednisolone equivalents) for treating grade ≥ 3 immune checkpoint inhibitor (ICI) hepatitis. The authors examined the effect of corticosteroid dosing on time to alanine aminotransferase (ALT) normalization, need for additional immunosuppression, and steroid-related complications.
Approach and results: They conducted a retrospective cohort study of 215 ICI-treated patients from 2010 to 2020 who developed grade ≥ 3 (ALT > 200 U/l) ICI hepatitis. Patients were grouped by initial corticosteroid dose (≥ 1.5 mg/kg or < 1.5 mg/kg methylprednisolone equivalents). Propensity scores were calculated predicting the risk of receiving the higher steroid dose and used in inverse probability of treatment-weighted (IPTW) logistic or Cox regression. The 87 patients in the ≥ 1.5 mg/kg group received higher initial (2.0 vs. 0.8 mg/kg/day, p < 0.001) and maximum (2.0 vs. 1.0 mg/kg/day, p < 0.001) steroid doses than the 128 patients in the < 1.5 mg/kg group. There was no difference between the higher- versus lower-dose groups in development of steroid-refractory hepatitis (odds ratio [OR] = 1.22, 95% confidence interval [CI]: 0.79–1.89, p = 0.365) on IPTW-logistic regression. In patients with steroid-responsive disease, there was no difference between the 2 groups in time to ALT normalization using either standard Cox regression (hazard ratio [HR] = 1.02, 95% CI: 0.72–1.45, p = 0.903) or IPTW-Cox regression (HR = 1.09, 95% CI: 0.78–1.51, p = 0.610). The ≥ 1.5 mg/kg group had longer exposure to corticosteroids (median 60 vs. 44 days, p = 0.005) and higher incidences of infection (18.4% vs. 7.0%, relative risk [RR] = 2.6, 95% CI: 1.2–5.6, p = 0.011) and hyperglycemia requiring treatment (23.3% vs. 7.8%, RR = 3.0, 95% CI: 1.5–6.0, p = 0.001).
Conclusions: In patients with high-grade immune checkpoint inhibitor hepatitis, initial treatment with 1 mg/kg/day methylprednisolone equivalents provides similar hepatitis outcomes with reduced risk of steroid-related complications when compared with higher-dose regimens.